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Twenty years ago, histone lysine demethylases (KDMs) were discovered. Since their discovery, they have been increasingly studied and shown to be important across species, development, and diseases. Considerable advances have been made toward understanding their (1) enzymology, (2) role as critical components of biological complexes, (3) role in normal cellular processes and functions, (4) implications in pathological conditions, and (5) therapeutic potential. This Review covers these key relationships related to the KDM field with the awareness that numerous laboratories have contributed to this field. The current knowledge coupled with future insights will shape our understanding about cell function, development, and disease onset and progression, which will allow for novel biomarkers to be identified and for optimal therapeutic options to be developed for KDM-related diseases in the years ahead.

Original publication

DOI

10.1016/j.cell.2025.02.023

Type

Journal

Cell

Publication Date

04/2025

Volume

188

Pages

1747 - 1783

Addresses

Cancer Epigenetics Institute, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Nuclear Dynamics and Cancer Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Biomedical Sciences Program, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Keywords

Animals, Humans, Histone Demethylases